Laminins are a family of basement membrane proteins which function in cell differentiation, adhesion, and migration, in addition to being true structural components (Tryggvason K, Curr. Opn. Cell Biol., 1993, 5:877-882, this and all following references are hereby incorporated by reference). The laminin molecule is a cross-shaped heterotrimer consisting of one heavy chain (.about.400 kd) and two light chains, .beta. and .gamma. (130-200 kd) (nomenclature according to Burgeson et al., Matrix Biol., 1994, 14:209-211). Laminin exists in numerous isoforms that are formed by different combinations of laminin chain variants which currently amount to at least nine.
Kalinin/laminin 5 (most likely also identical to the adhesion molecule nicein) is a recently identified laminin isoform which is a functional adhesion component for epithelial cells (Tryggvason, 1993, supra.; Burgeson et al., 1994, supra.; Rousselle et al., J. Cell Biol., 1991, 114:567-576; Kallunki et al., J. Cell Biol., 1992, 119:679-693; Marinkovich et al., J. Biol. Chem., 1992, 267:17900-17906; Vailly et al., Eur. J. Biochem., 1994, 219:209-218). Kalinin/laminin 5 contains unique laminin variant chains, one of which, the .gamma.2 chain, has recently been cloned and sequenced (Kallunki et al., 1992, supra., previously named B2t). The .gamma.2 chain has a mass of .about.130 kd and is thus smaller than the "classical" .about.200 kd .beta.1 and .gamma.1 light chains of laminin. The domain structure of the .gamma.2 chain also differs from that of the .gamma.1 chain in that it lacks the amino-terminal globular domain (domain VI) believed to function in intermolecular cross-linking of laminin molecules to form networks (Yurcheno and O'Rear, in Molecular and Celluar Aspects of Basement Membranes, 1993, (ed. Rohrbach and Timpl, Academic Press, San Diego, pp. 20-47). In addition, domains III, IV, and V (containing EGF-like repeats) in .gamma.2 are shorter than in the .gamma.1 chain (Kallunki et al., 1992, supra.).
By in situ hybridization the .gamma.2 chain was found to be expressed in epithelial cells of many embryonic tissues such as those of skin, lung, and kidney (Kallunki et al., 1992, supra.), and antibodies to kalinin/laminin 5, react with basement membranes of the same tissues (Rousselle et al., 1991, supra.; Verrando et al., Lab. Invest., 1991, 64:85-92).
The different laminin chains have been shown to have quite varying tissue distribution as determined by immunohistological studies, Northern, and in situ hybridization analyses. For example, the A and M chains on the one hand, and the B1 (.beta.1) and S (.beta.2) chains on the other, have been shown to be mutually exclusive (see for example Vuolteenaho et al., J. Cell Biol., 1994, 124:381-394). In vitro studies have indicated that laminin mediates a variety of biological functions such as stimulation of cell proliferation, cell adhesion, differentiation, and neurite outgrowth. The cellular activities are thought to be mediated by cell memebrane receptors, many of which are members of the integrin family (Ruoslahti, E. J. Clin. Invest., 1991, 87:1-5; Mecham, R. P. FASEB J., 1991, 5:2538-2546; Hynes, R. Cell, 1992, 69:11-25).
Recently a new nomenclature for describing laminins has been agreed to as in the following Table 1 (after Burgeson et al., 1994, supra.)
TABLE 1 ______________________________________ laminin chains and genes heterotrimers of laminin New Previous Gene New Chains Previous ______________________________________ .alpha.1 A, Ae LAMA1 laminin-1 .alpha.1.beta.1.gamma.1 EHS laminin .alpha.2 M, Am LAMA2 laminin-2 .alpha.2.beta.1.gamma.1 merosin .alpha.3 200 kDa LAMA3 laminin-3 .alpha.1.beta.2.gamma.1 s-laminin .beta.1 B1, B1e LAMB1 laminin-4 .alpha.2.beta.2.gamma.1 s-merosin .beta.2 S, B1s LAMB2 laminin-5 .alpha.3.beta.3.gamma.2 kalinin/nicein .beta.3 140 kDa LAMB3 laminin-6 .alpha.3.beta.1.gamma.1 k-laminin .gamma.1 B2, B2e LAMC1 laminin-7 .alpha.3.beta.2.gamma.1 ks-laminin .gamma.2 B2t LAMC2 ______________________________________